Acute and Prolonged Effects of 300 sec of Static, Dynamic, and Combined Stretching on Flexibility and Muscle Force.

Static stretching (SS), dynamic stretching (DS), and combined stretching (CS; i.e., DS+SS) are commonly performed as warm-up exercises. However, the stretching method with the greatest effect on flexibility and performance remains unclear. This randomized crossover trial examined acute and prolonged effects of SS, DS, and CS on range of motion (ROM), peak passive torque (PPT), passive stiffness, and isometric and concentric muscle forces. Twenty healthy young men performed 300 sec of active SS, DS, or CS (150-sec SS followed by 150-sec DS and 150-sec DS followed by 150-sec SS) of the right knee flexors on four separate days, in random order. Subsequently, we measured ROM, PPT, and passive stiffness during passive knee extension. We also measured maximum voluntary isometric and concentric knee flexion forces and surface electromyographic activities during force measurements immediately before, immediately after, and 20 and 60 min after stretching. All stretching methods significantly increased ROM and PPT, while significantly decreasing isometric knee flexion force (all p < 0.05). These changes lasted 60 min after all stretching methods; the increases in ROM and PPT and the decreases in isometric muscle force were similar. All stretching methods also significantly decreased passive stiffness immediately after stretching (all p < 0.05). Decreases in passive stiffness tended to be longer after CS than after SS or DS. Concentric muscle force was decreased after SS and CS (all p < 0.05). On the other hand, concentric muscle force was unchanged after DS, while the decreases in surface electromyographic activities during concentric force measurements after all stretching methods were similar. Our results suggest that 300 sec of SS, DS, and CS have different acute and prolonged effects on flexibility and muscle force.

Effects of High-Intensity Stretch with Moderate Pain and Maximal Intensity Stretch without Pain on Flexibility.

In this study, we aimed to identify the time course effects of different intensities of static stretch (SST) (maximal intensity without pain vs. high-intensity with moderate pain) on flexibility. This study included 16 healthy students (8 men and 8 women) who performed 1) 5-minute SST at 100%, 2) 110%, and 3) 120% intensity, as well as 4) no stretching (control) in a random sequence on four separate days. Static passive torque (SPT), hamstring electromyography (EMG), and pain intensity were continuously recorded during SST. We assessed markers of stiffness, range of motion (ROM), and maximal dynamic passive torque (DPTmax) before SST and 0, 15, 30, 45, 60, 75, and 90 minutes after SST. Stiffness decreased and ROM and DPTmax increased significantly immediately after SST at the three different intensity levels (p < 0.05). The effects of SST at 120% intensity were stronger and lasted longer than the effects of SST at 110% and 100% intensity (stiffness: -17%, -9%, and -7%, respectively; ROM: 14%, 10%, and 6%, respectively; DPTmax: 15%, 15%, and 9%, respectively). SPT decreased after SST at all intensities (p < 0.05). SST at 120% intensity caused a significantly greater reduction in SPT than SST at 100% intensity (p < 0.05). Pain intensity and EMG activity increased immediately after the onset of SST at 120% intensity (p < 0.05), although these responses were attenuated over time. Stretching intensity significantly correlated with the degree of change in ROM and stiffness (p < 0.05). These results support our hypothesis that stretch-induced flexibility is amplified and prolonged with an increase in stretch intensity beyond the pain threshold. Additional studies with more participants and different demographics are necessary to examine the generalizability of these findings.

Acute and chronic effects of static stretching at 100% versus 120% intensity on flexibility.

PURPOSE: The acute effects of static stretching have been frequently studied, but the chronic effects have not been studied concurrently. Thus, this study aimed to investigate both the acute and chronic effects of static stretching at different intensities on flexibility. METHODS: Twenty-three healthy men were randomly assigned to perform 1 min of static stretching 3 days/week for 4 weeks at 100% intensity (n = 12) or 120% intensity (n = 11). The acute effects of stretching were assessed by measuring the range of motion (ROM), peak passive torque, and passive stiffness before and after every stretching session; the chronic effects of stretching were assessed by measuring these outcomes at baseline and after 2 and 4 weeks of stretching. RESULTS: Compared with the 100% intensity group, the 120% intensity group had significantly greater acute increases in ROM after all 12 sessions, a significantly greater decrease in passive stiffness after 11 of 12 sessions, and a significantly greater increase in peak passive torque after six of 12 sessions. Regarding the chronic effects, ROM was significantly increased in both groups after 2 and 4 weeks of stretching. Peak passive torque significantly increased in the 100% intensity group after 2 and 4 weeks of stretching, and after 4 weeks in the 120% intensity group. CONCLUSION: Stretching at 120% intensity resulted in significantly greater acute improvements in ROM, peak passive torque, and stiffness than stretching at 100% intensity. Four weeks of stretching increased ROM and peak passive torque but did not decrease passive stiffness, regardless of the stretching intensity.

Median nerve injury does not contribute to early onset of decreased grip strength due to repetitive reaching and grasping tasks in rats.

BACKGROUND: Workplace risk factors, such as repetitive tasks, can cause work-related musculoskeletal disorders. In a rat model, decreased grip strength and median nerve injury develop following repetitive reaching and grasping tasks, involving negligible force. OBJECTIVE: We investigated whether median nerve injury is involved in the early onset of decreased grip strength due to such tasks METHODS: Sprague-Dawley rats were divided into: non-task-performing (0-week) and task-performing (1-, 2-, and 3-week) groups. After an initial training period, the task-performing groups continued to perform the task for 2 h/day, 3 days/week, for 1-3 weeks. Grip strength and relative muscle weight of the flexor digitorum superficialis (FDS) muscle were measured. Median nerve injury was evaluated by histopathology and immunohistochemistry. RESULTS: Grip strength of the reach limb (forelimb used in tasks) was significantly lower in the 3-week group compared with the other groups and was significantly lower than that of the non-reach limb in all groups. There were no significant differences in the relative FDS muscle weights of either limb among groups. No evidence of median nerve demyelination was observed and no cells expressed activating transcription factor-3, a specific marker of peripheral nerve injury, in the anterior horn of the spinal cord. CONCLUSION: Median nerve injury does not contribute to the decreased grip strength caused by 3 weeks of repetitive reaching and grasping tasks, involving negligible force, in rats.

The protective role of localized nitric oxide production during inflammation may be mediated by the heme oxygenase-1/carbon monoxide pathway.

Nitric oxide (NO) is an important part of the host defense mechanism; however, it displays both pro- and anti-inflammatory properties depending on its location and concentration. Importantly, excessive or inappropriate NO production can cause tissue damage. Systemic and local administration of NO synthase (NOS) inhibitors ameliorates and may exacerbate the inflammatory response, respectively. Here, we used a carrageenan-induced pleurisy model of acute inflammation in rats to confirm the location-dependent effects of NO and investigate the underlying mechanisms. As expected, localized suppression of NO production exacerbated inflammation, as evidenced by increased pleural exudate volumes and leukocyte counts and enhanced activity of enzymes related to oxidative stress. In contrast, local NO supplementation reduced leukocyte infiltration, vascular permeability, and the activity of oxidative stress-related enzymes. Interestingly, inhibition of heme oxygenase-1 (HO-1) reversed the anti-inflammatory effects of localized NO production, while the addition of hemin (HO-1 substrate) or carbon monoxide (CO; HO-1 metabolite) decreased leukocyte migration and exudation. Together, these findings confirm a protective role for NO at the inflammatory site, which appears to be mediated via NOS induction of the HO-1/CO pathway. Thus, NO supplementation may be a potential new treatment for oxidative stress-associated inflammatory diseases.

Changes in Flexibility and Force are not Different after Static Versus Dynamic Stretching.

In this study, we examined the effects of static and dynamic stretching on range of motion (ROM), passive torque (PT) at pain onset, passive stiffness, and isometric muscle force. We conducted a randomized crossover trial in which 16 healthy young men performed a total of 300 s of active static or dynamic stretching of the right knee flexors on two separate days in random order. To assess the effects of stretching, we measured the ROM, PT at pain onset, passive stiffness during passive knee extension, and maximum voluntary isometric knee flexion force using an isokinetic dynamometer immediately before and after stretching. Both static and dynamic stretching significantly increased the ROM and PT at pain onset (p<0.01) and significantly decreased the passive stiffness and isometric knee flexion force immediately after stretching (p<0.01). However, the magnitude of change did not differ between the two stretching methods for any measurements. Our results suggest that 300 s of either static or dynamic stretching can increase flexibility and decrease isometric muscle force; however, the effects of stretching do not appear to differ between the two stretching methods.

Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis.

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle.

Increased muscle contractile activity, as observed with regular exercise, prevents oxidative stress-induced muscle wasting, at least partially, by improving the antioxidant defense system. Phosphorylated p62/sequestosome1 competitively binds to the Kelch-like ECH-associated protein 1, activating nuclear factor erythroid 2-related factor 2 (Nrf2), which stimulates transcription of antioxidant/electrophile responsive elements. However, it remains to be determined if this process is activated by regular exercise in skeletal muscle. Here, we demonstrate that muscle contractile activity increases antioxidants, Nrf2 translocation into nuclei, and Nrf2 DNA-binding activity in association with increased p62 phosphorylation (Ser351) in mouse oxidative skeletal muscle. Skeletal muscle-specific loss of Nrf2 [i.e., Nrf2 muscle-specific knockout (mKO) mice] abolished the expression of the Nrf2 target antioxidant gene NAD(P)H-quinone oxidoreductase 1 (NQO1) in both glycolytic and oxidative muscles but reduced exercise-mediated increases of antioxidants (i.e., copper/zinc superoxide dismutase (SOD) and extracellular SOD only in oxidative muscle. Interestingly, skeletal muscle-specific loss of p62 (i.e., p62 mKO mice) also abolished the expression of NQO1 and reduced exercise-mediated increases of the same antioxidants in soleus muscle. Collectively, these findings indicate that p62 and Nrf2 cooperatively regulate the exercise-mediated increase of antioxidants in oxidative muscle.-Yamada, M., Iwata, M., Warabi, E., Oishi, H., Lira, V. A., Okutsu, M. p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle.

Dynamic Stretching Has Sustained Effects on Range of Motion and Passive Stiffness of the Hamstring Muscles.

Dynamic stretching (DS) is often performed during warm-up to help avoid hamstring muscle injuries, increase joint flexibility, and optimize performance. We examined the effects of DS of the hamstring muscles on passive knee extension range of motion (ROM), passive torque (PT) at the onset of pain (as a measure of stretch tolerance), and passive stiffness of the muscle-tendon unit over an extended period after stretching. Twenty-four healthy subjects participated, with 12 each in the experimental and control groups. Stretching was performed, and measurements were recorded using an isokinetic dynamometer pre-intervention, and at 0, 15, 30, 45, 60, 75, and 90 min post-intervention. DS consisted of ten 30-s sets of 15 repetitions of extension and relaxation of the hamstrings. ROM increased significantly (range, 7%-10%) immediately after DS, and the increase was sustained over 90 min. PT at the onset of pain also increased immediately by 10% but returned to baseline by 30 min. Passive stiffness decreased significantly (range, 7.9%-16.7%) immediately after DS, and the decrease was sustained over 90 min. Post-DS values were normalized to pre-DS values for the respective outcomes in both groups. ROM was significantly higher (range, 7.4%-10%) and passive stiffness was significantly lower (range, 5.4%-14.9%) in the experimental group relative to the control group at all time points. Normalized PT values at the onset of pain were significantly higher in the experimental group at 0-15 min than in the controls, but the differences were smaller at 30-45 min and not significant thereafter. We conclude that DS increases ROM and decreases passive stiffness in a sustained manner, and increases PT at the onset of pain for a shorter period. Overall, our results indicate that when performed prior to exercise, DS is beneficial for the hamstring muscles in terms of increasing flexibility and reducing stiffness.

Hamstring Stiffness Returns More Rapidly After Static Stretching Than Range of Motion, Stretch Tolerance, and Isometric Peak Torque.

Context: Hamstring injuries are common, and lack of hamstring flexibility may predispose to injury. Static stretching not only increases range of motion (ROM) but also results in reduced muscle strength after stretching. The effects of stretching on the hamstring muscles and the duration of these effects remain unclear. Objective: To determine the effects of static stretching on the hamstrings and the duration of these effects. Design: Randomized crossover study. Setting: University laboratory. Participants: A total of 24 healthy volunteers. Interventions: The torque-angle relationship (ROM, passive torque [PT] at the onset of pain, and passive stiffness) and isometric muscle force using an isokinetic dynamometer were measured. After a 60-minute rest, the ROM of the dynamometer was set at the maximum tolerable intensity; this position was maintained for 300 seconds, while static PT was measured continuously. The torque-angle relationship and isometric muscle force after rest periods of 10, 20, and 30 minutes were remeasured. Main Outcome Measures: Change in static PT during stretching and changes in ROM, PT at the onset of pain, passive stiffness, and isometric muscle force before stretching were compared with 10, 20, and 30 minutes after stretching. Results: Static PT decreased significantly during stretching. Passive stiffness decreased significantly 10 and 20 minutes after stretching, but there was no significant prestretching versus poststretching difference after 30 minutes. PT at the onset of pain and ROM increased significantly after stretching at all rest intervals, while isometric muscle force decreased significantly after all rest intervals. Conclusions: The effect of static stretching on passive stiffness of the hamstrings was not maintained as long as the changes in ROM, stretch tolerance, and isometric muscle force. Therefore, frequent stretching is necessary to improve the viscoelasticity of the muscle-tendon unit. Muscle force decreased for 30 minutes after stretching; this should be considered prior to activities requiring maximal muscle strength.

A novel tetracycline-responsive transgenic mouse strain for skeletal muscle-specific gene expression.

BACKGROUND: The tetracycline-responsive system (Tet-ON/OFF) has proven to be a valuable tool for manipulating gene expression in an inducible, temporal, and tissue-specific manner. The purpose of this study was to create and characterize a new transgenic mouse strain utilizing the human skeletal muscle α-actin (HSA) promoter to drive skeletal muscle-specific expression of the reverse tetracycline transactivator (rtTA) gene which we have designated as the HSA-rtTA mouse. METHODS: To confirm the HSA-rtTA mouse was capable of driving skeletal muscle-specific expression, we crossed the HSA-rtTA mouse with the tetracycline-responsive histone H2B-green fluorescent protein (H2B-GFP) transgenic mouse in order to label myonuclei. RESULTS: Reverse transcription-PCR confirmed skeletal muscle-specific expression of rtTA mRNA, while single-fiber analysis showed highly effective GFP labeling of myonuclei in both fast- and slow-twitch skeletal muscles. Pax7 immunohistochemistry of skeletal muscle cross-sections revealed no appreciable GFP expression in satellite cells. CONCLUSIONS: The HSA-rtTA transgenic mouse allows for robust, specific, and inducible gene expression across muscles of different fiber types. The HSA-rtTA mouse provides a powerful tool to manipulate gene expression in skeletal muscle.

Decreased grip strength, muscle pain, and atrophy occur in rats following long-term exposure to excessive repetitive motion.

Work-related musculoskeletal disorders (WMSD) are caused by the overuse of muscles in the workplace. Performing repetitive tasks is a primary risk factor for the development of WMSD. Many workers in highly repetitive jobs exhibit muscle pain and decline in handgrip strength, yet the mechanisms underlying these dysfunctions are poorly understood. In our study, rats performed voluntary repetitive reaching and grasping tasks (Task group), while Control group rats did not perform these activities. In the Task group, grip strength and forearm flexor withdrawal threshold declined significantly from week 2 to week 6, compared with these values at week 0 (P < 0.05). Relative muscle weight and muscle fiber cross-sectional area of flexor digitorum superficialis (FDS) muscles decreased significantly in the Task group, compared with the Control group, at 6 weeks (P < 0.05 and P < 0.01, respectively). Nerve growth factor, glial cell line-derived neurotrophic factor, and tumor necrosis factor α-expression in FDS muscles were not significantly different in Control and Task groups at 3 and 6 weeks. At 6 weeks, the Task group had elevated MuRF1 protein levels (P = 0.065) and significant overexpression of the autophagy-related (Atg) proteins, Beclin1 and Atg5-Atg12, compared with in the Control group (both P < 0.05). These data suggested that long-term exposure to excessive repetitive motion causes loss of grip strength, muscle pain, and skeletal muscle atrophy. Furthermore, this exposure may enhance protein degradation through both the ubiquitin-proteasome and autophagy-lysosome systems, thereby decreasing skeletal muscle mass.

Acute Effects of the Different Intensity of Static Stretching on Flexibility and Isometric Muscle Force.

Kataura, S, Suzuki, S, Matsuo, S, Hatano, G, Iwata, M, Yokoi, K, Tsuchida, W, Banno, Y, and Asai, Y. Acute effects of the different intensity of static stretching on flexibility and isometric muscle force. J Strength Cond Res 31(12): 3403-3410, 2017-In various fields, static stretching is commonly performed to improve flexibility, whereas the acute effects of different stretch intensities are unclear. Therefore, we investigated the acute effects of different stretch intensities on flexibility and muscle force. Eighteen healthy participants (9 men and 9 women) performed 180-second static stretches of the right hamstrings at 80, 100, and 120% of maximum tolerable intensity without stretching pain, in random order. The following outcomes were assessed as markers of lower limb function and flexibility: static passive torque (SPT), range of motion (ROM), passive joint (muscle-tendon) stiffness, passive torque (PT) at onset of pain, and isometric muscle force. Static passive torque was significantly decreased after all stretching intensities (p ≤ 0.05). Compared with before stretching at 100 and 120% intensities, ROM and PT were significantly increased after stretching (p ≤ 0.05), and passive stiffness (p = 0.05) and isometric muscle force (p ≤ 0.05) were significantly decreased. In addition, ROM was significantly greater after stretching at 100 and 120% than at 80%, and passive stiffness was significantly lower after 120% than after 80% (p ≤ 0.05). However, all measurements except SPT were unchanged after 80% intensity. There was a weak positive correlation between the intensities of stretching and the relative change for SPT (p ≤ 0.05), a moderate positive correlation with ROM (p ≤ 0.05), and a moderate positive correlation with passive stiffness (p ≤ 0.05). These results indicate that static stretching at greater intensity is more effective for increasing ROM and decreasing passive muscle-tendon stiffness.

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro.

It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid-induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid-induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel-like factor 15 (KLF15). Heat stress recovered the dexamethasone-induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress-induced protection against glucocorticoid-induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650-664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.

Changes in force and stiffness after static stretching of eccentrically-damaged hamstrings.

PURPOSE: This study compared responses to static stretching between eccentrically damaged and non-damaged muscles. METHODS: Twelve young men performed 60 maximum knee flexor eccentric contractions of one leg, and received a 300-s continuous passive static stretching at tolerable intensity without pain to both knee flexors at 2 and 4 days after the eccentric exercise. Range of motion (ROM) and passive stiffness during knee extension, passive torque at onset of pain (PT), maximum voluntary isometric (MVC-ISO) and isokinetic concentric contraction torque (MVC-CON), and visual analogue scale (VAS) for muscle soreness were measured before, immediately after, 60 min, 2 and 4 days after exercise as well as before, immediately after, 20 and 60 min after the stretching. Changes in these variables after eccentric exercise and stretching were compared between limbs. RESULTS: The eccentric exercise decreased MVC-ISO, MVC-CON, ROM and PT, and increased passive stiffness and VAS (p < 0.05), suggesting that muscle damage was induced to the knee flexors. ROM and PT increased after stretching for both limbs; however, the magnitude of the increase was greater (p < 0.05) for the damaged than non-damaged limb. Passive stiffness decreased for both limbs similarly (4-7 %) at immediately after stretching (p < 0.05). Significant decreases in MVC-ISO torque (7-11 %) after stretching were observed only for the non-damaged limb (p < 0.05), but MVC-CON torque did not change after stretching for both limbs. VAS decreased for the exercised limb after stretching (p < 0.05). CONCLUSIONS: These results suggest that the static stretching at tolerable intensity without pain produced greater positive effects on damaged than non-damaged muscles.

Acute effects of different stretching durations on passive torque, mobility, and isometric muscle force.

Static stretching is widely applied in various disciplines. However, the acute effects of different durations of stretching are unclear. Therefore, this study was designed to investigate the acute effects of different stretching durations on muscle function and flexibility, and provide an insight into the optimal duration of static stretching. This randomized crossover trial included 24 healthy students (17 men and 7 women) who stretched their right hamstrings for durations of 20, 60, 180, and 300 seconds in a random order. The following outcomes were assessed using an isokinetic dynamometer as markers of lower-limb function and flexibility: static passive torque (SPT), dynamic passive torque (DPT), stiffness, straight leg raise (SLR), and isometric muscle force. Static passive torque was significantly decreased after all stretching durations (p < 0.05). Static passive torque was significantly lower after 60, 180, and 300 seconds of stretching compared with that after 20-second stretching, and stiffness decreased significantly after 180- and 300-second stretching (p < 0.05). In addition, DPT and stiffness were significantly lower after 300 seconds than after 20-second stretching (p < 0.05), and SLR increased significantly after all stretching durations (p < 0.05). Straight leg raise was higher after 180- and 300-second stretching than after 20-second stretching and higher after 300-second stretching than after 60-second stretching (p < 0.05). Isometric muscle force significantly decreased after all stretching durations (p < 0.05). Therefore, increased duration of stretching is associated with a decrease in SPT but an increase in SLR. Over 180 seconds of stretching was required to decrease DPT and stiffness, but isometric muscle force decreased regardless of the stretching duration. In conclusion, these results indicate that longer durations of stretching are needed to provide better flexibility.

A Nondestructive Evaluation Method: Measuring the Fixed Strength of Spot-Welded Joint Points by Surface Electrical Resistivity.

Destructive tests are generally applied to evaluate the fixed strength of spot-welding nuggets of zinc-plated steel (which is a widely used primary structural material for automobiles). These destructive tests, however, are expensive and time-consuming. This paper proposes a nondestructive method for evaluating the fixed strength of the welded joints using surface electrical resistance. A direct current nugget-tester and probes have been developed by the authors for this purpose. The proposed nondestructive method uses the relative decrease in surface electrical resistance, α. The proposed method also considers the effect of the corona bond. The nugget diameter is estimated by two factors: RQuota, which is calculated from variation of resistance, and a constant that represents the area of the corona bond. Since the maximum tensile strength is correlated with the nugget diameter, it can be inferred from the estimated nugget diameter. When appropriate measuring conditions for the surface electrical resistance are chosen, the proposed method can effectively evaluate the fixed strength of the spot-welded joints even if the steel sheet is zinc-plated.

Therapeutic potential of ASP3258, a selective phosphodiesterase 4 inhibitor, on chronic eosinophilic airway inflammation.

We investigated and compared the pharmacological effects of a PDE4 inhibitor ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), with those of roflumilast, the most clinically advanced PDE4 inhibitor known. ASP3258 inhibited human PDE4A, 4B, 4C, and 4D with respective IC(50) values of 0.036, 0.050, 0.45, and 0.035 nmol/l, all approximately 3-6 times more potent than roflumilast. ASP3258 inhibited LPS-induced TNF-α production and PHA-induced IL-5 production in human whole blood cells with respective IC(50) values of 110 and 100 nmol/l, both approximately 10 times less potent than roflumilast. Repeatedly administered ASP3258 and roflumilast both suppressed chronic airway eosinophilia induced by repeated exposure to ovalbumin in Brown Norway rats with respective ED(50) values of 0.092 and 0.17 mg/kg. We also evaluated the toxicological profiles of ASP3258. Although PDE4 inhibitors induce emesis by mimicking the pharmacological action of an α(2)-adrenoceptor antagonist, repeated administration of ASP3258 (3 mg/kg) had no such inhibitory effect on rats anesthetized with α(2) - adrenoceptor agonist. PDE4 inhibitors are also known to induce vascular injury in rats. Although repeatedly administered ASP3258 (3 and 10 mg/kg) significantly increased plasma fibrinogen, a biomarker for toxicity, 1 mg/kg of ASP3258 did not. These results suggest that ASP3258 is an attractive PDE4 inhibitor for treating chronic eosinophilic airway inflammation due to asthma.

Evaluation of a newly-developed immunochromatography strip test for diagnosing dermatophytosis.

BACKGROUND: Traditionally, dermatophytosis, a common disease affecting millions of people world-wide, has been diagnosed by direct microscopy and fungal culture. The immunochromatography (ICG) strip test was recently developed. METHODS: We compared the performance of the ICG strip test for the detection of dermatophytes in samples from human skin and nails with direct microscopy. The 160 samples, consisting of 88 skin and 72 nail specimens, were subjected to direct microscopy study using a 20% KOH solution and to examination with the ICG strip test. Of 160 samples, 18 were examined by fungal culture using Sabouraud dextrose agar medium. RESULTS: We found that the overall sensitivity and specificity of the ICG test were 83.5% and 66.7%; they were 82.1% and 76.2% for the 88 skin and 85.4% and 58.3% for the 72 nail specimens, respectively. CONCLUSIONS: Our findings indicate that the efficacy of the ICG test is comparable to direct microscopy for the detection of dermatophytes. Performance of the assay was easy, and results were available quickly. We suggest that it is an effective tool for dermatophytosis screening.

Anti-neutrophilic inflammatory activity of ASP3258, a novel phosphodiesterase type 4 inhibitor.

Neutrophil-dominant pulmonary inflammation is an important feature of chronic obstructive pulmonary disease (COPD). Here, we evaluated the in vitro and in vivo anti-neutrophilic inflammatory activities of ASP3258, a novel, orally active, and selective phosphodiesterase (PDE) 4 inhibitor with anti-inflammatory potency comparable to that of second-generation compound roflumilast but with lower emetic activity in vivo. In in vitro experiments using human peripheral blood neutrophils, PDE4 inhibitors ASP3258, cilomilast, and roflumilast inhibited fMLP-induced superoxide production in a concentration-dependent manner with IC50 values of 5.0, 96, and 4.7 nM, respectively. ASP3258, cilomilast, and roflumilast also attenuated fMLP-induced neutrophil chemotaxis in a concentration-dependent manner with IC30 values of 18, 270, and 9.7 nM, respectively. In contrast, the glucocorticoid prednisolone inhibited neither superoxide production nor chemotaxis up to 1 µM. In a rat model of lipopolysaccharide (LPS)-induced lung inflammation, orally administered ASP3258, cilomilast, roflumilast, and prednisolone (at 10 or 30 mg/kg) dose-dependently attenuated pulmonary accumulation of neutrophils. The inhibitory effect of ASP3258 was more potent than cilomilast and almost the same as roflumilast and prednisolone. Treatment with ASP3258 inhibited the elevation of TNF-α in the bronchoalveolar lavage fluid following LPS instillation. Histological examination revealed significant inhibition of neutrophil and macrophage infiltration into alveoli by ASP3258. Overall, these findings suggest that ASP3258 has therapeutic potential for treating neutrophilic inflammation such as COPD, partly through direct inhibition of neutrophil activation as well as possibly through inhibition of the TNF-α-mediated pathway.