The sea urchin, Paracentrotus lividus, as a model to investigate the onset of molecules immunologically related to the α-7 subunit of nicotinic receptors during embryonic and larval development

Nicotinic acetylcholine receptors play a major role in the regulation of electrochemical synapses at neuromuscular junctions. During the early stages of Paracentrotus lividus development, the nicotinic receptor-like molecules are found and localized by use of the specific blocker, -bungarotoxin, and by α-7 subunit immunoreactivity. Both the methods identify and localize the nicotinic receptor-like molecules at the sites where active changes in ionic intracellular concentration take place. These are well known to lead either fertilization, sperm propulsion or co-ordinated ciliary movement. After neural differentiation, immunoreactivity for the α-7 subunit is localized mainly in ganglia, ectoderm ciliary bands and in the motile cells forming the gut wall. Both α-bungarotoxin binding sites and α-7 subunits are also localized at the cells linked to the skeletal rods, performing the small movements which drive the swimming direction in the water column. The localization of these molecules paves the way to a speculation on their function and possible role in neurogenesis as well as neurodegeneration.     

Role of advanced oxidation protein products and Thiol ratio in patients with acute coronary syndromes

ObjectivesTo identify systemically detectable vascular inflammation associated to redox system unbalance, advanced oxidation protein products (AOPP), formed by HClO reaction with proteins, Thiol levels, and their ratio (AOPP/Thiol ratio) were measured in patients with acute coronary syndromes (ACS).Design and methodsWe evaluated AOPP/Thiol ratio together with CRP and IL-1β in 18 acute myocardial infarction (AMI) and in 16 unstable angina (UA) patients at admission, and in 16 control subjects (CTR); the measurements were repeated at 1 and at 6 months.ResultsAt admission, AMI and UA patients displayed higher AOPP/Thiol ratio and CRP and IL-1β compared to CTR subjects. A correlation between AOPP/Thiols and IL-1β in AMI was found. At follow-up, in UA only, AOPP/Thiol ratio and IL-1β levels still remained high.ConclusionsThe AOPP/Thiol ratio seems to affect the inflammatory process in ACS, and may represent a reliable marker of oxidative unbalance in this setting of patients.     

Fentanyl buccal tablets for breakthrough pain in highly tolerant cancer patients: preliminary data on the proportionality between breakthrough pain dose and background dose

Context

Cancer patients receiving high doses of opioids as background medication are challenging, and it would be useful clinically to know whether a rapid-onset opioid (ROO) for breakthrough cancer pain (BTcP) may be started at a dose proportional to the background opioid dose.

Objectives

The aim of this study was to assess the efficacy and safety of the fentanyl buccal tablet (FBT) in doses proportional to the opioid dose administered for background analgesia in a sample of patients with BTcP who were receiving high doses of opioids.

Methods

Twelve patients who were receiving opioids for background analgesia at doses equivalent to more than 500 mg of oral morphine and had adequately controlled pain were prospectively recruited. BTcP was treated with proportional doses of FBT: patients receiving 600 mg of oral morphine equivalents were administered 1000 μg of FBT, patients receiving 900 mg of oral morphine equivalents were administered 1500 μg of FBT, and so on. For each episode of BTcP, trained nurses collected pain intensity (on a 0–10 numerical rating scale) and emerging problems when called for increases in pain considered to be severe in intensity by patients (T0) and 15 minutes after FBT administration (T15).

Results

Patients were receiving mean doses of oral morphine equivalents of 1340 mg (±585; range 720–2400). Seventy-nine events were treated with FBT (6.6 ± 4.9 for each patient). The median pain intensity of BTcP events was 8 (range 7–10), and the mean dose of FBT administered was 2233 μg (±975; range 1200–4000). In most events, a decrease in pain intensity >33% and >50% was observed (n = 14 and n = 48, respectively) 15 minutes after the administration of FBT. Data on 11 episodes were missed. Only six events were unsuccessfully treated. In all the patients, the level of adverse effects after FBT administration was mild and indistinguishable from that associated with the background opioid analgesia.

Conclusion

FBT in doses proportional to the high doses of opioids used for background analgesia was efficacious and well tolerated when administered for BTcP. Controlled studies with a specific design and a large number of patients should confirm such preliminary results.     

Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.