Effect of microcystin-LR on protein phosphatase 2A and its function in human amniotic epithelial cells

Due to their toxicity, the increased distribution of microcystins (MCs) has become an important worldwide problem. MCs have been recognized as inhibitors of protein phosphatase 2A (PP2A) through their binding to the PP2A catalytic subunit. However, the exact mechanism of MC toxicity has not been elucidated, especially concerning the cellular response and its autoregulation. To further dissect the role of PP2A in MC-induced toxicity, the present study was undertaken to determine the response of PP2A in human amniotic epithelial (FL) cells treated with microcystin-LR (MCLR), one of the MC congeners. The results show that a low-dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity, and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A, as expected. The increased mRNA and protein levels of the PP2A C subunit may explain the increased activity of PP2A. Furthermore, MCLR altered microtubule post-translational modifications through PP2A. These results further clarify the underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the complex toxicity of MCLR.     

拯救生命的给予

大多数的人总是倾向于临渴挖井而非居安思危,总觉得那些不幸之事不会降临到自己身上,但是大家有没有想过,也许有一天躺在病床上苦苦等待别人救助的会变成我们自己或者我们亲友?我是那些幸运儿之一,现在轮到我去帮助别人了。我最近进行了一次奇妙的旅行,刚从南非的德班回来,我在那里参加了第19届世界移植运动会。自1996年起,我就一直有参加这个移植运动会。无论怎么看,我     

A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats

Radiation therapy has been widely applied in cancer treatment. However, it often causes thrombocytopenia (deficiency of white blood cells) as an adverse effect. Recombinant human interleukin-6 (rhIL-6) has been found to be a very effective way against this thrombocytopenia, but IL-6 has low stability in blood, which reduces its efficacy. To increases the stability and half-life of rhIL-6, it was modified by polyethylene glycol (PEG). The pharmacokinetics and the tissue distribution of PEG-rhIL-6 labeled with ¹²⁵I were examined after subcutaneous injection in rats. The pharmacokinetic pattern of PEG-rhIL-6 was defined with linear-kinetics, and we fitted a one-compartment model with half-lives of 10.44–11.37 h (absorption, t _{1/2K a}) and 19.77–21.53 h (elimination, t _1/2Ke), and peak concentrations at 20.51–21.96 h (t _peak) in rats. Half-lives and t _peak of PEG-rhIL-6 were longer than those of rhIL-6 previously reported. In the present study, for deposition of PEG-rhIL-6 in rats, the tissue distribution examination showed that blood was the major organ involved, rather than liver. However, as to the elimination of PEG-rhIL-6, the major organ was the kidney. The excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous administration. Less than 6% of PEG-rhIL-6 was eliminated via the feces at 192 h. These results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.     

The role of upper torso and pelvis rotation in driving performance during the golf swing

While the role of the upper torso and pelvis in driving performance is anecdotally appreciated by golf instructors, their actual biomechanical role is unclear. The aims of this study were to describe upper torso and pelvis rotation and velocity during the golf swing and determine their role in ball velocity. One hundred recreational golfers underwent a biomechanical golf swing analysis using their own driver. Upper torso and pelvic rotation and velocity, and torso-pelvic separation and velocity, were measured for each swing. Ball velocity was assessed with a golf launch monitor. Group differences (groups based on ball velocity) and moderate relationships (r > or = 0.50; P < 0.001) were observed between an increase in ball velocity and the following variables: increased torso-pelvic separation at the top of the swing, maximum torso-pelvic separation, maximum upper torso rotation velocity, upper torso rotational velocity at lead arm parallel and last 40 ms before impact, maximum torso-pelvic separation velocity and torso-pelvic separation velocity at both lead arm parallel and at the last 40 ms before impact. Torso-pelvic separation contributes to greater upper torso rotation velocity and torso-pelvic separation velocity during the downswing, ultimately contributing to greater ball velocity. Golf instructors can consider increasing ball velocity by maximizing separation between the upper torso and pelvis at the top of and initiation of the downswing.     

Changes in the prevalence of child sexual abuse, its risk factors, and their associations as a function of age cohort in a Finnish population sample

Objective

We examined (1) the prevalence of childhood sexual abuse (CSA) experiences as a function of cohort and gender, (2) the prevalence of factors associated with CSA as a function of cohort and whether the association of these factors with CSA remained the same irrespective of cohort, and (3) whether any cohort differences could be explainable by cohort differences in reporting bias.

Method

We used the responses of 4,561 men (M = 29, SD = 7 years) and 8,361 female (M = 29, SD = 7 years) Finnish participants who responded to the Childhood Trauma Questionnaire-Short Form as well as questions regarding family structure.

Results

The prevalence of CSA experiences varied between 0.7-4.6% for men and 1.8-7.5% for women depending on the item. Younger cohorts reported less CSA as well as less of the risk factors (physical neglect and abuse, emotional neglect and abuse, parental substances abuse, not growing up with both biological parents) that were positively associated with the likelihood of CSA. The effects of these risk factors did not vary as a function of the cohort. Also, the declining trend was not explainable by social desirability being higher in the younger cohorts.

Conclusions

The results suggest that there is a real decline in the prevalence of CSA and it is associated with a simultaneous decline in factors associated with CSA.     

Muscle fatigue induced by exercise simulating the work rate of competitive soccer

Fatigue represents a reduction in the capability of muscle to generate force. The aim of the present study was to establish the effects of exercise that simulates the work rate of competitive soccer players on the strength of the knee extensors and knee flexors. Thirteen amateur soccer players (age 23.3+/-3.9 years, height 1.78+/-0.05 m, body mass 74.8+/-3.6 kg; mean+/-s) were tested during the 2000-2001 soccer season. Muscle strength of the quadriceps and hamstrings was measured on an isokinetic dynamometer. A 90 min soccer-specific intermittent exercise protocol, incorporating a 15 min half-time intermission, was developed to provide fatiguing exercise corresponding in work rate to a game of soccer. The exercise protocol, performed on a programmable motorized treadmill, consisted of the different intensities observed during soccer match-play (e.g. walking, jogging, running, sprinting). Muscle strength was assessed before exercise, at half-time and immediately after exercise. A repeated-measures analysis of variance showed significant reductions (P < 0.001) in peak torque for both the quadriceps and hamstrings at all angular velocities (concentric: 1.05, 2.09, 5.23 rad x s(-1); eccentric: 2.09 rad x s(-1)). The peak torque of the knee extensors (KE) and knee flexors (KF) was greater before exercise [KE: 232+/-37, 182+/-34, 129+/-27, 219+/-41 N x m at 1.05, 2.09 and 5.23 rad x s(-1) (concentric) and 2.09 rad x s(-1) (eccentric), respectively; KF: 126+/-20, 112+/-19, 101+/-16, 137+/-23 N x m] than at half-time (KE: 209+/-45, 177+/-35, 125+/-36, 214+/-43 N x m; KF: 114+/-31, 102+/-20, 92+/-15, 125+/-25 N x m) and greater at half-time than after exercise (KE: 196+/-43, 167+/-35, 118+/-24, 204+/-43 N x m; KF: 104+/-25, 95+/-21, 87+/-13, 114+/-27 N x m). For the hamstrings:quadriceps ratio, significant changes were found (P < 0.05) for both legs, the ratio being greater before than after exercise. For fast:slow speed and left:right ratios, no significant changes were found. We conclude that there is a progressive reduction in muscle strength that applies across a range of functional characteristics during exercise that mimics the work rate in soccer.