Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia

INTRODUCTION: Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM. METHODS: Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value. RESULTS: Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion. CONCLUSIONS: Our results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle

TGF-β1 stimulation and VDR-dependent activation modulate calcitriol action on skeletal muscle fibroblasts and Smad signalling-associated fibrogenesis

Abstract Fibroblasts play a pivotal role in fibrogenesis after skeletal muscle injury. Excess fibrous formation can disrupt contractile functions and delay functional recovery. Although vitamin D receptor (VDR) is expressed explicitly in regenerating muscle compared with uninjured muscle, how calcitriol [1α,25(OH)2D3] directly regulates skeletal muscle primary fibroblast proliferation, the transition to myofibroblasts, and Smad signalling-associated fibrogenesis is currently unknown. Herein, the effects of calcitriol on cultured skeletal muscle primary fibroblasts of male C57BL/6 mice (aged 1 month old) were investigated. The percentage of BrdU+ nuclei in primary fibroblasts was significantly decreased after calcitriol treatment; however, the antiproliferative effect of calcitriol was diminished after TGF-β1 stimulation to induce fibroblast to myofibroblast transition. This suppressive effect was associated with significantly decreased VDR expression in TGF-β1-treated cells. In addition, Vdr siRNA transfection abolished the effects of calcitriol on the suppression of α-SMA expression and Smad2/3 signalling in myofibroblasts, supporting that its antifibrogenic effect requires VDR activation. Compared with calcitriol, the antifibrotic agent suramin could inhibit fibroblast/myofibroblast proliferation and suppress the expression of TCF-4, which regulates fibrogenic determination. Collectively, these findings suggest that profibrotic stimulation and VDR-dependent activation could modulate the effects of calcitriol on skeletal muscle fibroblast proliferation and fibrogenesis processes. Therefore, TGF-β1 and VDR expression levels are crucial determinants for the antifibrogenic effect of calcitriol on skeletal muscle after injury

Residual lung volume of female Thai adults

ABSTRACT: Lung volumes including residual volume (RV) are ethnicity-dependent parameters which are useful in clinical diagnosis of lung diseases and in assessing body density, and hence total body adiposity. The latter predisposes an individual to cardiovascular and/or metabolic diseases which are serious health problems worldwide. At present, RV of Thai people has not been reported. This study determines RV of young adult Thai women and proposes a prediction equation to compare it with other equations previously reported for the Asian population. A group of 161 healthy young women aged between 18 and 29 years were recruited for constructing and cross-validating the equation. RV was measured by an O2 dilution technique using a computerized spectrometer. Anthropometric variables were determined using a beam balance, a stadiometer, and bioelectric impedance analysis. The mean residual volume for the selected group of young Thai women is 1.18 ± 0.23 l and best described by the equation RV = −3.236 + 0.024H + 0.028A where H is the height in cm and A is the age in years. Goldman and Becklake’s equation for Caucasians overestimated our RV whereas those of Ching and Horsfall, and Demura et al for Chinese and Japanese people, respectively, underestimated it. Chin’s equation for Singaporeans yields similar value to the measured residual volume. The results confirm that residual volume is ethnically and geographically dependent. The equations for Thais and Singaporean of the same age and sex are comparable

Effectiveness of losartan on infrapatellar fat pad/synovial fibrosis and pain behavior in the monoiodoacetate-induced rat model of osteoarthritis pain

Infrapatellar fat pad (IFP)/ synovial fibrosis is closely associated with the clinical symptoms of joint pain and stiffness, which contribute to locomotor restriction in osteoarthritis (OA) patients. Hence, this study was designed to gain insight on whether losartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has therapeutic benefit to reverse IFP/synovial fibrosis and secondarily to attenuate pain behavior. In male Wistar rats with monoiodoacetic acid (MIA)-induced IFP/synovial fibrosis, a possible role for increased AT1R expression in the pathogenesis of IFP/synovial fibrosis was assessed over an 8-week period. Pain behavior comprised static weight bearing and von Frey paw withdrawal thresholds (PWTs), which were assessed once or twice weekly, respectively. Groups of MIA-rats received oral losartan (30-mg/kg; n = 8 or 100-mg/kg; n = 9) or vehicle (n = 9) for 28-days according to a prevention protocol. Animals were euthanized on day 28 and various tissues (IFP/synovium, cartilage and lumbar dorsal root ganglia (DRGs)) were collected for histological, immunohistochemical and western blot analyses. Administration of once-daily losartan for 28-days dose-dependently attenuated the development of static weight bearing. This was accompanied by reduced IFP/synovial fibrosis and suppression of TGF-β1 expression. Chronic treatment of MIA-rats with losartan had an anti-fibrotic effect and it attenuated pain behavior in this animal model

Additional file 1: Table S1. of Modulating effects of exercise training regimen on skeletal muscle properties in female polo ponies

Muscle fiber type I obtained after different periods of exercise training and activities. (DOCX 20 kb

Correction: Inducible Cre transgenic mouse strain for skeletal muscle-specific gene targeting

BACKGROUND: The use of the Cre/loxP system for gene targeting has been proven to be a powerful tool for understanding gene function. The purpose of this study was to create and characterize an inducible, skeletal muscle-specific Cre transgenic mouse strain. METHODS: To achieve skeletal muscle-specific expression, the human α-skeletal actin promoter was used to drive expression of a chimeric Cre recombinase containing two mutated estrogen receptor ligand-binding domains. RESULTS: Western blot analysis, PCR and β-galactosidase staining confirmed that Cre-mediated recombination was restricted to limb and craniofacial skeletal muscles only after tamoxifen administration. CONCLUSIONS: A transgenic mouse was created that allows inducible, gene targeting of floxed genes in adult skeletal muscle of different developmental origins. This new mouse will be of great utility to the skeletal muscle community