Yukisato Ishida

Roles of Basic Amino Acid Residues in the Activity of μ‐Conotoxin GIIIA and GIIIB, Peptide Blockers of Muscle Sodium Channels

To study in detail the roles of basic amino acid residues in the activity of μ‐conotoxin GIIIA (μ‐GIIIA) and GIIIB (μ‐GIIIB), specific blockers of muscle sodium channels, seven analogs of μ‐GIIIA, and two analogs of μ‐GIIIB were synthesized. μ‐GIIIA analogs were synthesized by replacing systematically the three Arg residues (Arg1, Arg13, and Arg19) with one, two, and three Lys residues. μ‐GIIIB analogs were synthesized by replacing simultaneously all four Lys residues (Lys9, Lys11, Lys16, and Lys19) with Arg residues and further replacement of acidic Asp residues with neutral Ala residues. Circular dichroism spectra of the synthesized analogs suggested that the replacement did not affect the three dimensional structure. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the side chain guanidino group of Arg13 of μ‐GIIIA was important for the activity, whereas that of Arg19 had little role for biological activity. Although [Arg9,11,16,19]μ‐GIIIB showed higher activity than native μ‐GIIIB, highly basic [Ala2,12, Arg9,11,16,19]μ‐GIIIB showed lower activity, suggesting that there was an appropriate molecular basicity for the maximum activity.

Changes in the Width of the Tibiofibular Syndesmosis Related to Lower Extremity Joint Dynamics and Neuromuscular Coordination on Drop Landing During the Menstrual Cycle

Background: Many injuries of the lower extremities, especially the knee and ankle, occur during sports activity, and the incidence rate is higher in women than in men. Hypothesis: The hypothesis was that phases of the menstrual cycle affect the width of the tibiofibular syndesmosis during drop landing in healthy young women and that such changes at the tibiofibular joint also affect the dynamics and neuromuscular coordination of the lower extremities. Study Design: Descriptive laboratory study. Methods: Participants included 28 healthy young women (mean age, 21.0 ± 0.8 years). Blood samples were collected to determine plasma levels of estradiol and progesterone immediately before the performance of the task: drop landing on a single leg from a 30-cm platform. Using ultrasonography, the distance between the tibia and the distal end of the fibula, regarded as the width of the tibiofibular syndesmosis, was measured in an upright position without flexion of the ankle. The peak ground-reaction force (GRF) on landing was measured using a force platform. The time to peak GRF (Tp-GRF) was measured as the time from initial ground contact to the peak GRF. Hip, knee, and ankle joint angles during the single-leg landing were calculated using a 3-dimensional motion analysis system. Muscle activities of the lower extremities were measured using surface electromyography. Results: The width of the tibiofibular syndesmosis was significantly greater in the luteal phase when compared with the menstrual, follicular, and ovulation phases (by 5%-8% of control). Also, during the luteal phase, the Tp-GRF was significantly shorter than in the follicular phase (by 6%); hip internal rotation and knee valgus were significantly greater than in the menstrual phase (by 43% and 34%, respectively); knee flexion was significantly less than in the menstrual and follicular phases (by 7%-9%); ankle dorsiflection was significantly less than in the follicular phase (by 11%); ankle adduction and eversion were significantly greater than in the menstrual and follicular phases (by 26%-46%, and 27%-33%, respectively); and activation of the gluteus maximus before landing was significantly lower than in the menstrual and follicular phases (by 20%-22%). Conclusion: The luteal phase appears to be associated with decreased strength and laxity of the ankle as well as lower extremity muscle activity in women. The changes presumably represent a greater risk for sports injuries. Clinical Relevance: The results of this study suggest that the luteal phase may be related to the greater incidence of lower extremity injuries in women.

Instantaneous changes in respiratory function induced by passive pelvic suspension in the supine position in relation to increased diaphragm excursion

[Purpose] This study aimed to introduce an approach of pelvic suspension (PS) using sling cords and to obtain evidence for changes in respiratory function of healthy subjects. [Subjects and Methods] Subjects were 25 healthy men. In the supine position, with hip and knee joints flexed at 90°, the subjects’ pelvises were suspended with sling belts. Diaphragm excursion, respiratory function, and respiratory comfort in these postures were measured using ultrasonography, respirometry, and visual analog scale (VAS), respectively. [Results] When the pelvis was passively suspended with sling cords, the diaphragm moved 5 mm cranially and diaphragm excursion showed an instantaneous increase compared with the control. The tidal volume (VT) showed an increase and the respiration rate (RR) showed a decrease. The extent of diaphragm excursion was correlated with changes in VT under the control and PS conditions. Independent measurements of pulmonary function revealed that PS reduced the expiratory reserve volume, being correlated positively and negatively to increases in vital and inspiratory capacities, respectively. Furthermore, VAS values for respiratory ease were greater with PS than with the control. [Conclusion] These results suggest that PS effectively changed diaphragm excursion and respiratory function, leading to ease of breathing (i.e., deep and slow respiration).

Gender difference in distance of tibiofibular syndesmosis to joint dynamics of lower extremities during squat

The incidence of lower extremity injury is greater in women than men, indicating gender difference in lower extremity function. Here we investigate the role of the ankle during squatting in young men and women by measuring the tibiofibular syndesmosis (TFS) distance and the angles of hip, ankle and knee joints. TFS distance was positively correlated to body mass in men, but not in women, suggesting some factor(s) affecting TSF distance in women. When divided into two groups with wide and narrow TFS distances, men apparently used ankle and hip joints evenly during squatting, but women, specifically those with a narrow TFS distance, used the hip joint more effectively than ankle. Estimated knee moment was positively correlated to TFS distance in women, but not in men. These results suggest that the women possessing a wider TFS distance use ankle function rather than hip junction when performing lower-extremity exercises (i.e. squatting), presumably accounting for the higher incidence of ankle injury in women during such activities.

Pulse pressure to vascular cells: novel methods for solving pathogenesis in cell migration.

Vascular smooth muscle migration is a risk factor for developing atherosclerosis, a major cause of morbidity and mortality. A cohort study carried out over 25 years in seven countries revealed that pulse pressure, diastolic and systolic pressures are the best predictors of cardiovascular disease death.1 In this issue of Cardiovascular Research , Tada et al. (Shimokawas group) describe a novel method using a newly developed apparatus that enables determination of the pulse pressure-loading onto vascular smooth muscle cells using Boyden chambers.2 This new avenue for in vitro experiments to simulate the in situ pulse pressure in the systemic circulation has now been opened to elucidate the cellular and molecular mechanisms involved in how the pulse pressure affects smooth muscle migration processes. Tada et al. showed that migration of cultured aortic … *Corresponding author. Tel: + 81 49 261 7943; fax: + 81 49 261 8923. E-mail address : ishiday{at}hst.u-bunkyo.ac.jp