Calmodulin loss in vascular smooth muscle following Triton X-100 or saponin skinning

The calmodulin (CaM) content of intact and chemically skinned strips of rat caudal artery was measured using a¹²⁵I-CaM radioimmunoassay. The total CaM measured following homogenization of arterial tissue with EGTA and EGTA/Triton X-100 was 2.58 mol/kg wet tissue. Based on a smooth muscle volume of 40%, this value corresponds to a cellular CaM concentration of 6.5 M. Approximately 97% of total CaM was soluble and approximately 3% was EGTA-nonextractable. Permeabilization of the plasmalemma with 0.15 mg/ml saponin or 0.5% Triton X-100 caused significant detergent-dependent loss of CaM. At the end of a 1 h skinning period, tissues exposed to saponin lost 30% of total CaM. By comparison, tissues skinned under the same conditions with Triton X-100 lost 50%. During a subsequent 4h exposure to relaxing solution, total tissue CaM continued to decline. The exponential loss over the 5h period was described by a first order model having diffusible and nondiffusible CaM components. The diffusible CaM component of saponin skinned tissue (59%) was significantly less than the diffusible component of those skinned with Triton X-100 (88%); however, the rate coefficients for CaM diffusion (0.78 h^–1 and 0.91 h^–1, respectively) did not statistically differ. The nondiffusible component of CaM was significantly larger in saponin treated strips (42%) than in Triton X-100 permeabilized tissue (12%). Arterial strips skinned with Triton X-100, which were subsequently exposed to relaxing solution for up to 22 h, lost significantly more CaM than those retained in Triton X-100 skinning solution for a comparable duration These studies demonstrate the diffusion of CaM from detergent skinned arterial strips and characterize the time course of that loss.     

Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia

Excitatory amino acid neurotransmitters have been implicated in fostering brain edema and neuronal death in ischemia. As both of these processes are involved in nervous system damage during neonatal anoxia, the effect of blockade of cell excitation with kynurenate upon brain water was studied following anoxic-ischemic brain injury in neonatal rats. Such treatment attenuated brain edema immediately after, and 24 h following anoxia-ischemia.     

Water-clear-cell hyperplasia mimicking parathyroid adenoma

The case of a patient with primary hyperparathyroidism in whom water-clear-cell hyperplasia (WCCH) involved only the superior glands, and disproportionately so, is presented. In addition, unlike the cases of WCCH described previously, a rim of normal parathyroid tissue was observed at the periphery of each gland in this case. It is speculated that these findings are not necessarily peculiar, but may reflect an earlier stage of the disease. Such cases may mimic parathyroid adenoma, thereby leading to inadequate surgical therapy.     

MR imaging with surface coils

The use of specialized coils to improve signal-to-noise ratios in magnetic resonance (MR) imaging is an important innovation. The role of surface coils has not yet been well defined, but it seems likely that they will be routinely used for clinical imaging of the orbit, neck, and spine. Surface coils have important limitations that make other designs, such as "closely coupled" volume coils, attractive for some applications, especially for limb imaging. With improvement in our ability to visualize anatomy with MR imaging, specialized radio frequency coils may provide new imaging capabilities for clinical problems that were not previously considered to be indications for diagnostic imaging.     

Protective role of thiols in carcinogen-induced DNA damage in rat liver

Biological thiols are known to play an important role in thedetoxification of xenobiotics, including chemical carcinogens.To determine the influence of cellular thiols on carcinogeninduction of hepatic DNA damage in the rat, diethylmaleate (DEM)administration was used to deplete intracellular gluta-thione(GSH). The effects of administration of the synthetic thiols,N-acetylcysteine (NAC) and alpha-mercaptopropionyl-glycine (MPG),on the induction of DNA lesions were also examined. Pretreatmentwith DEM reduced liver GSH levels by >70%. As assessed bythe technique of alkaline elution, subsequent administrationof N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) resulted inDNA damage 4 h post MNNG treatment which was 4- to 8-fold greaterthan that induced in the livers of rats treated with MNNG alone.However, DEM pretreatment had little effect on the extent ofDNA damage induced by methylnitrosourea (MNU). DEM alone didnot cause any measurable DNA damage. Pretreatment with MPG orNAC reduced MNNG-induced DNA damage by as much as 77%. In contrast,MNU-induced DNA damage was increased by MPG treatment whereasNAC treatment was without effect. These results indicated thatin the rat liver, the activity of some DNA alkylating agentsmay be modulated in varying degree by the concentration of intracellularthiols. These data support the notion that thiols play an importantrole in protection against carcinogen damage, and that syntheticthiols such as MPG and NAC may be useful as anti-carcinogenicagents against certain carcinogens.     

The Application of Creatine Supplementation in Medical Rehabilitation

Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders. Several of the findings are encouraging, showcasing creatine’s potential efficacy as a supplemental agent via preservation of muscle mass, strength, and physical function; however, the results are not consistent. For multiple diseases, only a few creatine studies with small sample sizes have been published, making it difficult to draw definitive conclusions. Rationale for discordant findings is further complicated by differences in disease pathologies, intervention protocols, creatine dosing and duration, and patient population. While creatine supplementation demonstrates promise as a therapeutic aid, more research is needed to fill gaps in knowledge within medical rehabilitation.     

The Hunger Games: Homeostatic State-Dependent Fluctuations in Disinhibition Measured with a Novel Gamified Test Battery

Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours.     

Work factors facilitating working beyond state pension age: Prospective cohort study with register follow-up

Objectives:The demographic changes in Europe underline the need for an extension of working lives. This study investigates the importance of physical work demands and psychosocial work factors for working beyond the state pension age (65 years).Methods:We combined data from three cohorts of the general working population in Denmark (DWECS 2005 and 2010, and DANES 2008), where actively employed workers aged 55–59 years replied to questionnaires about work environment and were followed until the age of 66 years in the Danish AMRun register of paid employment. Using logistic regression analyses, we calculated prevalence ratios (PR) and 95% confidence intervals (CI) for the association between physical and psychosocial work factors and working beyond state pension age, adjusted for age, sex, cohort, cohabiting, sector, income, vocational education, working hours, lifestyle, and previous sickness absence.Results:Of the 2884 workers aged 55–59 years, 1023 (35.5%) worked beyond the state pension age. Higher physical work demands was associated with a lower likelihood (PR 0.69, 95% CI 0.58–0.82) and a good psychosocial work environment was associated with higher likelihood (average of 7 items: PR 1.81, 95% CI 1.49–2.20) of working beyond state pension age. Stratified analyses did not change the overall pattern, ie, a good overall psychosocial work environment – as well as several specific psychosocial factors – increased the likelihood of working beyond state pension age, both for those with physically active and seated work.Conclusion:While high physical work demands was a barrier, a good psychosocial work environment seems to facilitate working beyond state pension age, also for those with physically active work.