Effect of polychlorinated biphenyls on several endocrine reproductive parameters in the female rhesus monkey

Female rhesus monkeys (Macaca mulatto) ingested gelatin capsules containing daily doses of 0 (control), 5, 20, 40, or 80 g of Aroclor® 1254/kg/day (PCB) which was dissolved in corn oil plus glycerol. After approximately two years of dosing and when the monkeys were near an adipose tissue PCBs equilibrium, each dose group of 16 animals was randomly divided into two test groups. Daily blood samples from both groups were acquired for estrogen and progesterone analysis during one menstrual cycle. Test group 1 was sampled during February-March and test group 2 during August–September. Serum estrogen and progesterone concentrations in monkeys dosed with PCBs were equivalent to control values with the exception of the luteal phase progesterone levels in the 20 and 80 g/kg/day dosed monkeys in test group 1. There was no difference in menstrual cycle length between control and treated monkeys for the month sampled, however, menses duration was marginally longer in the 80 g/kg/day dose group. There were no apparent treatment related differences in the incidence of anovulatory cycles nor on the temporal relationship between the estrogen peak and menses onset, menses end or the progesterone peak.     

Postural adjustments for online corrections of arm movements in standing humans

The aim of this study was to investigate how humans correct ongoing arm movements while standing. Specifically, we sought to understand whether the postural adjustments in the legs required for online corrections of arm movements are predictive or rely on feedback from the moving limb. To answer this question we measured online corrections in arm and leg muscles during pointing movements while standing. Nine healthy right-handed subjects reached with their dominant arm to a visual target in front of them and aligned with their midline. In some trials, the position of the target would switch from the central target to one of the other targets located 15°, 30°, or 45° to the right of the central (midline) target. For each target correction, we measured the time at which arm kinematics, ground reaction forces, and arm and leg muscle electromyogram significantly changed in response to the target displacement. Results show that postural adjustments in the left leg preceded kinematic corrections in the limb. The corrective postural muscle activity in the left leg consistently preceded the corrective reaching muscle activity in the right arm. Our results demonstrate that corrections of arm movements in response to target displacement during stance are preceded by postural adjustments in the leg contralateral to the direction of target shift. Furthermore, postural adjustments preceded both the hand trajectory correction and the arm-muscle activity responsible for it, which suggests that the central nervous system does not depend on feedback from the moving arm to modify body posture during voluntary movement. Instead, postural adjustments lead the online correction in the arm the same way they lead the initiation of voluntary arm movements. This suggests that forward models for voluntary movements executed during stance incorporate commands for posture that are produced on the basis of the required task demands.     

No one listens to me,nobody believes me: Self management and the experience of living with encephalitis

Over the past twenty years, there has been considerable interest in individuals’ experience of chronic illness. In addition to the more established concerns of medical sociology, recent policy reflects an interest in how individuals manage their condition. Using material from qualitative interviews with 23 individuals carried out in the United Kingdom, this paper examines a person’s experience following encephalitis, as a way of exploring the potential value of current policy initiatives associated with self-management. Our findings suggest that individuals’ illness experiences become embedded in conditional acceptance derived from and sustained through their social relationships. This raises a fundamental policy tension: is the purpose of current self-management strategies to help individuals cope better with illness or with the context in which their illness experience is realised? We conclude that policy needs to question how it ‘imagines’ long-standing conditions, without recourse to generalised notions of coping and adjustment. This, in turn, means adapting a less instrumental and more contextualised approach to self-management.     

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.     

BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571

Clinical studies have shown that the tyrosine kinase inhibitor STI571 effectively controls BCR-ABL-positive chronic myelogenous leukemia (CML). However, disease progression while on STI571 therapy has been reported, suggesting de novo or intrinsic resistance to BCR-ABL-targeted therapy. To investigate possible mediators of acquired STI571 resistance, K562 cells resistant to 5 microM STI571 (K562-R) were cloned and compared to the parental cell population. K562-R cells had reduced BCR-ABL expression and limited activation of BCR-ABL signaling cascades (Stat 5, CrkL, MAPK). STI571 failed to activate caspase cascades or to suppress expression of survival genes (bcl-xL) in resistant cells. Gene sequencing and tyrosine kinase activity measurements demonstrated that K562-R cells retained wild-type and active BCR-ABL tyrosine kinase that was inhibitable by in vitro incubation with STI571, suggesting that BCR-ABL was not coupled to proliferation or survival of K562-R cells. The src-related kinase LYN was highly overexpressed and activated in K562-R cells, and its inhibition reduced proliferation and survival of K562-R cells while having limited effects of K562 cells. Specimens taken from patients with advanced CML that progressed on STI571 therapy also were analyzed for LYN kinase expression, and they were found to be elevated to a level similar to that of K562-R cells. Comparison of samples from patients taken prior to and following STI571 failure suggested that expression and/or activation of LYN/HCK occurs during disease progression. Together, these results suggest that acquired STI571 resistance may be associated with BCR-ABL independence and mediated in part through overexpression of other tyrosine kinases.     

Preliminary effect of projectile yaw on extremity gunshot wounding in a cadaveric animal model: a serendipitous study

International Journal of Legal Medicine - Gunshot wounding (GSW) is capable of causing devastating tissue injuries by delivering kinetic energy (KE) through the contact surface area of a...     

Standing up from a chair as a dynamic equilibrium task: a comparison between young and elderly subjects

The purpose of this study was to analyze and compare the features of center of mass (CoM) control along anterior/posterior axis in young and elderly subjects during sit-to-stand (STS). From a sitting position, seven healthy young subjects and seven healthy elderly subjects were asked to stand up from a chair under different experimental conditions (visual conditions: normal and blindfolded; speed: normal and as fast as possible). Analysis of results was based upon the concept of a "dynamic equilibrium area" (DEA), which in turn identified the dynamic limits of balance. The results showed that both the maximal CoM velocity in the horizontal axis and the CoM velocity at the instant of seat-off were found to be lower in elderly compared with young subjects. Concerning the maximal CoM velocity, the difference was increased under blindfolded condition. The position of CoM in the phase plane (i.e., velocity according to displacement) at the instant of seat-off was found to be shifted backward in elderly subjects. From these results we can deduce that age-related modifications can he observed in the control of the horizontal CoM motion during STS in healthy elderly subjects.     

Relative improvements in endurance performance with age: evidence from 25 years of Hawaii Ironman racing

Despite of the growth of ultra-endurance sports events (of duration >6 h) over the previous few decades, the age-related declines in ultra-endurance performance have drawn little attention. The aim of the study was to analyse the changes in participation and performance trends of older (>40 years of age) triathletes between 1986 and 2010 at the Hawaii Ironman triathlon consisting of 3.8 km swimming, 180 km cycling and 42 km running. Swimming, cycling, running and total times of the best male and female triathletes between 18 and 69 years of age who competed in the Hawaii Ironman triathlon were analysed. The relative participation of master triathletes increased during the 1986–2010 period, while the participation of triathletes younger than 40 years of age decreased. Linear regression showed that males older than 44 years and females older than 40 years significantly improved their performances in the three disciplines and in the total time taken to complete the race. Gender differences in total time performance significantly decreased in the same time period for all age groups between the 40–44 and 55–59 years ones. The reasons for these relative improvements of Ironman athlete performances in older age groups remain, however, unknown. Further studies investigating training regimes, competition experience or sociodemographic factors are needed to gain better insights into the phenomenon of increasing participation and improvement of ultra-endurance performance with advancing age.