Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. The signal transducer and activation of transcription 6 (STAT6) is one of the major signal transducers activated by IL-13, and a possible involvement of IL-13/STAT6 pathway in the augmented bronchial smooth muscle (BSM) contraction has been suggested. In the present study, the effect of a novel STAT6 inhibitor, AS1517499, on the development of antigen-induced BSM hyperresponsiveness was investigated. In cultured human BSM cells, IL-13 (100 ng/ml) caused a phosphorylation of STAT6 and an up-regulation of RhoA, a monomeric GTPase responsible for Ca2+ sensitization of smooth muscle contraction: both events were inhibited by co-incubation with AS1517499 (100 nM). In BALB/c mice that were actively sensitized and repeatedly challenged with ovalbumin antigen, an increased IL-13 level in bronchoalveolar lavage fluids and a phosphorylation of STAT6 in bronchial tissues were observed after the last antigen challenge. These mice had an augmented BSM contractility to acetylcholine together with an up-regulation of RhoA in bronchial tissues. Intraperitoneal injections of AS1517499 (10 mg/kg) 1 hour before each ovalbumin exposure inhibited both the antigen-induced up-regulation of RhoA and BSM hyperresponsiveness, almost completely. A partial but significant inhibition of antigen-induced production of IL-13 was also found. These findings suggest that the inhibitory effects of STAT6 inhibitory agents, such as AS1517499, both on RhoA and IL-13 up-regulations might be useful for asthma treatment.
To compare the efficacy and adherence rates of two parallel home exercise therapy programs-multiple exercise (training and stretching the knee and hip muscles) and control (training the quadriceps muscles)-on knee pain, physical function, and knee extension strength in community-dwelling elderly individuals with pre-radiographic knee osteoarthritis (OA). One hundred patients with medial knee pain were randomly allocated to one of two 4-week home exercise programs. Individuals with a Kellgren/Lawrence (K/L) grade 0 or 1 OA (pre-radiographic knee OA) in the medial compartment were enrolled. Primary outcomes were knee pain (visual analog scale), self-reported physical function (Japanese Knee Osteoarthritis Measure [JKOM]), and isometric maximum muscle strength of the knee extensor measured using a hand-held dynamometer. A total of 52 patients (28 [53.8%] in the multiple exercise group, 24 [46.2%] in the control group) completed the trial. The JKOM activities of daily living and general health conditions outcomes improved significantly in the multiple exercise group compared to the control group (JKOM activities of daily living, beta = - 0.76; 95% confidence interval [CI], - 1.39 to - 0.13; p = 0.01; JKOM general health conditions, beta = - 0.25; 95% CI, - 0.48 to - 0.01; p = 0.03). The home exercise compliance rates of the multiple exercise and control groups were 96.6 and 100%, respectively. When targeting pre-radiographic knee OA in community-dwelling elderly, it is important to implement home exercise programs that aim to improve muscle strength and joint flexibility rather than knee extension muscle power only.
[Purpose] This study aimed to clarify the effects of Capacitive and Resistive electric transfer (CRet) on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise. [Subjects and Methods] Twenty-two healthy males were assigned into either the CRet (n=11) or control (n=11) group. Fatiguing exercise and CRet intervention were applied at the quadriceps muscle of the participants’ dominant legs. The Ely test, pelvic tilt, lumbar lordosis, and superficial temperature were measured before and after exercise and for 30 minutes after intervention. Statistical analysis was performed using one-way analysis of variance, with Tukey’s post-hoc multiple comparison test to clarify within-group changes and Student’s t-test to clarify between-group differences. [Results] The Ely test and pelvic tilt were significantly different in both groups after exercise, but there was no difference in the CRet group after intervention. Superficial temperature significantly increased in the CRet group for 30 minutes after intervention, in contrast to after the exercise and intervention in the control group. There was no significant between-group difference at any timepoint, except in superficial temperature. [Conclusion] CRet could effectively improve muscle flexibility and lumbopelvic alignment after fatiguing exercise.
[Purpose] Few studies on the transverse arch (TA) in the forefoot have been conducted. The forefoot is where pains occur most frequently and is related to walking and balance; hence, paying attention to TA is vital. However, the relationship between TA and foot muscles has not been investigated. Therefore, this study aims to investigate muscles related to TA. [Subjects and Methods] Nineteen healthy young males were included. Measurements of their feet, excluding one foot with recent foot pain (n=37), were obtained. The height of TA (TAH) was measured in two ways: during 10% and 90% loading of body weight. The cross-sectional area and thickness of five muscles were measured: flexor digitorum longus, peroneus longus and brevis, flexor hallucis brevis, flexor digitorum brevis (FDB) and abductor hallucis (ABH). All measurements were performed with an ultrasound device. [Results] FDB and ABH were correlated with TAH during 10% and 90% loading after removing the effect of body mass index and age. The greater FDB and ABH, the higher TAH. [Conclusion] As FDB becomes larger, the second, third and fourth metatarsal heads are raised more. Furthermore, the height of the first metatarsal head is lowered by a larger ABH. These mechanisms may increase TAH.
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