Role of Wake‐Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep‐Promoting Effects of Ethanol

Background: Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake‐promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol‐induced sleep associated with the inhibition of the BF wake‐promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep‐promoting effects of ethanol? Methods: To address these questions, we performed 3 experiments in Sprague–Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c‐Fos expression (a marker of neuronal activation) in the BF wake‐promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol‐induced sleep. Results: Significant increase in non‐rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake‐promoting neurons with c‐Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8‐cyclopentyl‐1, 3‐dipropylxanthine into the BF significantly attenuated sleep‐promoting effects of ethanol. Conclusion: These results suggest that the inhibition of BF wake‐promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol.     

Beta-carotene micellarization during in vitro digestion and uptake by Caco-2 cells is directly proportional to beta-carotene content in different genotypes of cassava

Cassava, a staple food in sub-Saharan Africa, does not provide adequate amounts of pro-vitamin A (VA) carotenoids and has been targeted for biofortification (i.e. selectively breeding cultivars of increased nutrient density with agroeconomically acceptable characteristics). However, the accessibility of pro-VA carotenoids for absorption in different cultivars of cassava remains unknown. Here, we used the coupled in vitro digestion/Caco-2 cell uptake model to screen the relative accessibility of beta-carotene (betaC) in 10 cultivars of cassava with varying concentrations of betaC. After cooking (boiled for 30 min), the betaC concentration in tubers from different cultivars ranged from less than detectable to 6.9 microg betaC/g cassava. Samples were subjected to simulated oral, gastric, and small intestinal digestion to determine stability and micellarization of betaC. All-trans betaC, 9-cis betaC, and 13-cis betaC were the most abundant carotenoids in cooked cassava and recoveries after digestion exceeded 70%. Efficiency of micellarization of total betaC was 30 +/- 2% for various cultivars with no significant difference in isomers and linearly proportional to concentration in cooked cassava (r = 0.87; P < 0.001). Accumulation of all-trans betaC by Caco-2 cells incubated with the diluted micelle fraction for 4 h was proportional (R(2) = 0.99; P < 0.001) to the quantity present in micelles. These results suggest that all-trans betaC content appears to provide the key selection marker for breeding cassava to improve VA status and that the more complicated screening procedure using in vitro digestion coupled to cell uptake does not provide additional information on potential bioavailability.     

Rostral and dorsal anterior cingulate cortex make dissociable contributions during antisaccade error commission

The anterior cingulate cortex (ACC) participates in both performance optimization and evaluation, with dissociable contributions from dorsal (dACC) and rostral (rACC) regions. Deactivation in rACC and other default-mode regions is important for performance optimization, whereas increased rACC and dACC activation contributes to performance evaluation. Errors activate both rACC and dACC. We propose that this activation reflects differential error-related involvement of rACC and dACC during both performance optimization and evaluation, and that these two processes can be distinguished by the timing of their occurrence within a trial. We compared correct and error antisaccade trials. We expected errors to correlate with an early failure of rACC deactivation and increased activation of both rACC and dACC later in the trial. Eighteen healthy subjects performed a series of prosaccade and antisaccade trials during event-related functional MRI. We estimated the hemodynamic responses for error and correct antisaccades using a finite impulse-response model. We examined ACC activity by comparing error and correct antisaccades with a fixation baseline and error to correct antisaccades directly. Compared with correct antisaccades, errors were characterized by an early bilateral failure of deactivation of rACC and other default-mode regions. This difference was significant in rACC. Errors also were associated with increased activity in both rACC and dACC later in the trial. These results show that accurate performance involves deactivation of the rACC and other default mode regions and suggest that both rACC and dACC contribute to the evaluation of error responses.     

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n?=?15) had definite PAH; group 2 (n?=?19) had interstitial lung disease (ILD); group 3 (n?=?30) were SSc-controls; and group 4 (n?=?34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0?±?85.4 vs 380.4?±?168.3 ng/mL, p?=?0.136), SSc-controls (263.0?±?85.4 vs 253.1?±?98.0 ng/mL, p?=?1.00), or healthy controls (263.0?±?85.4 vs 201.8?±?57.2 ng/mL, p?=?0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2?±?434.9 vs 1424.8?±?527.6 ng/mL, p?=?1.00) and SSc-controls (1476.2?±?434.9 vs 1409.5?±?341.1 ng/mL, p?=?1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4?±?134.0 vs 201.8?±?57.2 ng/mL, p?<?0.0001) and VCAM-1 compared to healthy controls (1432.7?±?427.4 vs 1125.6?±?273.4 ng/mL, p?<?0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.     

A 24-year old man with persistent progressive breathlessness: early onset COPD.

We describe the case of a 24-year old male who had been a heavy smoker since the age of 9 and who presented with an 8-year history of respiratory symptoms. He was having treatment for asthma. Spirometric studies and high-resolution computed tomography (HRCT) scans confirmed COPD with centrilobular emphysema. His blood level of alpha-1-antitrypsin was within the normal range. Early onset emphysema in smokers with a normal alpha-1-antitrypsin has been previously described. However, this case is, as far as we know, one of the youngest cases ever reported.     

Spectrum of high-resolution MRI findings in diabetic neuropathy

OBJECTIVE: Diabetes is the most common cause of neuropathy. Focal diabetic neuropathy, although less common than entrapment neuropathy, clinically mimics entrapment neuropathy. This article depicts the spectrum of MR abnormalities in diabetic subjects- from abnormal T2 hyperintensity and fascicular enlargement in the acute and subacute stages to atrophic-appearing fascicles with intraepineurial fat deposition in the chronic stage-on high-resolution high-field (3-T) MRI. CONCLUSION: A spectrum of imaging abnormalities is observed in diabetic neuropathy. It is important for radiologists to understand the pathophysiology and recognize high-resolution MR appearances of these lesions and of related entities in the differential diagnosis for appropriate diagnosis and patient treatment.     

Protrusio acetabuli and total hip arthroplasty in patients with Marfan syndrome

Our goals were (1) to quantify protrusio acetabuli in patients with Marfan syndrome who underwent total hip arthroplasty and (2) to identify clinical results and complications associated with total hip arthroplasty in those patients. We reviewed the preoperative radiographs of the 29 patients (38 hips) in our study and analyzed the related patient operative reports, postoperative records, and self-administered questionnaires (mean follow-up, 116 ± 102 months). The mean preoperative center-edge angle of Wiberg was 50.9° ± 14°. Loosening (3) and radiolucent lines (4) occurred in femoral but not acetabular components. The hips had 15 complications, including 8 reoperations. High questionnaire scores (82 ± 13 points) indicated good hip function regardless of preoperative protrusio severity.