Pathophysiologic mechanisms in REM sleep behavior disorder

REM sleep behavior disorder (RBD) is a fascinating experiment in nature predicted by animal studies in 1964. A defining feature of REM sleep is active paralysis of all somatic musculature (sparing the diaphragm to permit respiration). RBD is characterized by the absence of REM atonia, permitting the appearance of dream-enacting behaviors. These oneiric behaviors may be violent or injurious. RBD typically affects men over the age of 50 years. Longitudinal follow-up has shown that the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative disorders, most notably one of the synucleinopathies (Parkinson’s disease, dementia with Lewy body disease, multiple system atrophy, or pure autonomic failure), often after a prolonged interval lasting more than 10 years. RBD is also a common manifestation of narcolepsy. RBD may be induced by medications, especially the tricyclic antidepressants and serotonin-specific reuptake inhibitors. In most cases, clonazepam is a highly effective treatment.     

Simvastatin protects against cholestasis-induced liver injury

Background:

Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. The aim of this study was to evaluate the effect of simvastatin on cholestasis-induced liver inflammation and tissue damage.

Experimental approach:

C57BL/6 mice were treated with simvastatin (0.02 and 0.2 mg·kg⁻¹) and vehicle before and after undergoing bile duct ligation (BDL) for 12 h. Leukocyte recruitment and microvascular perfusion in the liver were analysed using intravital fluorescence microscopy. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also determined.

Key results:

Administration of 0.2 mg·kg⁻¹ simvastatin decreased ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin reduced hepatic formation of CXC chemokines by 37–82% and restored sinusoidal perfusion in cholestatic animals. Moreover, BDL-induced leukocyte adhesion in sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was significantly reduced by simvastatin. Notably, administration of 0.2 mg·kg⁻¹ simvastatin 2 h after BDL induction also decreased cholestatic liver injury and inflammation.

Conclusions and implications:

These findings show that simvastatin protects against BDL-induced liver injury. The hepatoprotective effect of simvastatin is mediated, at least in part, by reduced formation of CXC chemokines and leukocyte recruitment. Thus, our novel data suggest that the use of statins may be an effective strategy to protect against the hepatic injury associated with obstructive jaundice.     

Visual discrimination and short-term memory for random patterns in patients with a focal cortical lesion

Visual discrimination and short-term recognition memory for computer- generated random patterns were explored in 23 patients with a postsurgical lesion in one of the cortical hemispheres. Their results are compared with those of 23 age-matched volunteers. In a same- different forced-choice discrimination task, d' and log beta (measures of sensitivity and bias), as well as reaction time (RT) were determined. All participants viewed patterns defined either by luminance contrast or isoluminant red-green color contrast, the amplitude of which was adjusted to be 10 times the respective detection threshold level. Block patterns consisting of a 6 x 6 matrix of light and dark (red and green) checks were randomly configured on each presentation. They were presented in pairs, randomly in two visual quadrants for a duration of 200 msec. Three presentation conditions were used: simultaneous presentation of reference and test stimulus, sequential presentation with a short delay (interstimulus interval, ISI = 3 s), and sequential presentation with a long delay (ISI = 6 s). The results indicate that patients with a lesion in the occipitotemporal cortex, the superior temporal cortex and the frontal cortex were significantly impaired on both luminance-contrast and color-contrast pattern discrimination. Patients with damage in the anterior inferotemporal cortex showed no overall impairment. The results suggest that performance in visual discrimination and recognition memory tasks rely on distributed neural processes with more than one neocortical location.      

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165