Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool

European Archives of Psychiatry and Clinical Neuroscience - Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical...     

Corticospinal excitability in human subjects during nonrapid eye movement sleep: single and paired-pulse transcranial magnetic stimulation study

The mechanisms responsible for changes in brain function during normal sleep are poorly understood. In this study, we aimed to investigate the effects of sleep on human corticospinal excitability by estimating resting motor threshold (RMT), and latency and amplitude of motor-evoked potentials (MEPs) after delivering transcranial magnetic stimulation (TMS) in ten healthy subjects. We also aimed to study short-interval intracortical inhibition (SICI) during sleep with paired-pulse TMS (pp-TMS). Ten healthy volunteers were studied. They were monitored immediately before, during and after a 3-h sleep (from 1 p.m. to 4 p.m., immediately after the mid-day meal). EEG was continuously recorded during sleep and the various sleep stages were identified off line. Every 10 min, subjects received ten single stimuli (to estimate RMT, MEP latency and amplitude) and six paired stimuli (to estimate SICI). MEP amplitude decreased and latency and RMT increased during the various sleep stages and returned to baseline values on awakening. Post hoc comparisons showed a significant difference in pp-TMS MEP amplitudes between the sleep and all the other conditions. The changes in TMS evoked variables during the different sleep stages indicate that during nonrapid eye movement sleep, cortical pyramidal neuron excitability (as measured by RMT, MEP latency and amplitude) progressively diminishes and the efficiency of the intracortical GABA-ergic network (as assessed by three pp-TMS) increases. On awakening, these sleep-induced changes in corticospinal excitability return rapidly to values observed during wakefulness.     

EEG and fMRI Coregistration to Investigate the Cortical Oscillatory Activities During Finger Movement

Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during␣fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.     

New tools for the control of peptide conformation: the helicogenic Cα‐methyl,Cα‐cyclohexylglycine*

Abstract: The novel C^α‐tetrasubstituted α‐amino acid C^α‐methyl, C^α‐cyclohexylglycine was prepared by hydrogenation of its C^α‐methyl, C^α‐phenylglycine precursor. Terminally protected homodi‐, homotri‐, and homotetrapeptides from C^α‐methyl, C^α‐cyclohexylglycine and co‐oligopeptides to the pentamer level in combination with Gly or α‐aminoisobutyric acid residues were prepared by solution methods and fully characterized. The results of a conformational analysis, performed by use of Fourier transform infrared (FT‐IR) spectrophotomet absorption, ¹H NMR, and X‐ray diffraction techniques, support the contention that this C^α‐methylated, C^β‐trisubstituted aliphatic α‐amino acid is an effective β‐turn and 3₁₀‐helix inducer in tri‐ and longer peptides as its C^α‐methyl valine parent compound, but partially divergent from the corresponding aromatic C^α‐methyl, C^α‐diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers.     

Cystic meningioma simulating glioblastoma in x-ray computed tomography

Seven cases of supratentorial meningiomas are reported. CT-Scan showed irregular hypo-hyperdense zones and features of intratumoral cysts. At surgery a well circumscribed tumor has always been found and easily removed "en bloc". In two cases stereotaxic biopsy was performed previously. CT-Scan findings of meningiomas with microcystic structure and/or necrotic areas may mimic a malignant glioma and lead to an incorrect presumptive diagnosis: then, both therapy and prognosis will be very different. It comes that stereotaxic biopsy is mandatory in all suspected cases of cerebral tumors, in the absence of classical angiographic patterns.     

(αMe)Aun: a highly lipophilic,chiral, Cα‐tetrasubstituted α‐amino acid. Incorporation into model peptides and preferred conformation

Abstract: Using a chemo‐enzymatic approach we prepared the highly lipophilic, chiral, C^α‐methylated α‐amino acid (αMe)Aun. Two series of terminally protected model peptides containing either d ‐(αMe)Aun in combination with Aib or l ‐(αMe)Aun in combination with Gly were synthesized using solution methods and fully characterized. A detailed solution conformational analysis, based on FT‐IR absorption, ¹H NMR and CD techniques, allowed us to determine the preferred conformation of this amino acid and the relationship between chirality at its α‐carbon atom and screw sense of the helix that is formed. The results obtained strongly support the view that d ‐(αMe)Aun favors the formation of the left‐handed 3₁₀‐helical conformation.     

Structural features of linear,homo‐Aib‐based peptides in solution: a spectroscopic and molecular mechanics investigation

Abstract: In continuation of our studies on the determination of the structural features of functionalized peptides in solution by combining time‐resolved fluorescence data and molecular mechanics results, the conformational properties of a series of linear, homo‐Aib peptides in methanol (a structure‐supporting solvent) were investigated. These compounds have the general formula P(Aib)_nN, where Aib is α‐aminoisobutyric acid, N is naphthalene and P is the monomethylated protoporphyrin IX, the two latter chromophores being covalently attached to the peptide C‐ and N‐termini, respectively, while n = 3, 6 and 9. According to ¹H NMR and IR spectra, the peptides investigated largely populate a 3₁₀‐helical structure in CDCl₃, which is also a structure‐supporting solvent. Both steady‐state and time‐resolved fluorescence measurements show a strong quenching of the N emission that parallels an increase of the P fluorescence intensity, suggesting the occurrence of long‐range energy transfer from ¹N* to ground‐state P. Comparison of quenching efficiencies and lifetime pre‐exponents with those obtained theoretically from the deepest energy minimum conformers is very satisfactory. The computed structures, built up by partially taking into account the solvent medium, exhibit a rigid, highly compact arrangement, owing to both the 3₁₀‐helix conformation of the backbone chain and the very few peptide‐to‐chromophore covalent linkages. As a result, only one or two stable conformations for each peptide were theoretically found, in full agreement with the time‐resolved fluorescence data. Orientational effects between the probes must be taken into account for a correct interpretation of the fluorescence decay results, which implies that interconversion among conformational substates of the N linkages is slower than 10 ns, corresponding to the upper limit of the energy transfer
characteristic time.     

Ac10c: a medium‐ring,cycloaliphatic Cα,α‐disubstituted glycine. Incorporation into model peptides and preferred conformation

Abstract: Two complete series of N‐protected oligopeptide esters to the pentamer level from 1‐amino‐cyclodecane‐1‐carboxylic acid (Ac₁₀c), an α‐amino acid conformationally constrained through a medium‐ring C^α_i ? C^α_i cyclization, and either the l ‐Ala or Aib residue, along with the N‐protected Ac₁₀c monomer and homo‐dimer alkylamides, were synthesized using solution methods and fully characterized. The preferred conformation of these model peptides was assessed in deuterochloroform solution using FT‐IR absorption and ¹H NMR techniques. Furthermore, the molecular structures of two derivatives (Z‐Ac₁₀c‐OH and Fmoc‐Ac₁₀c‐OH) and two peptides (the dipeptide ester Z‐Ac₁₀c‐l ‐Phe‐OMe and the tripeptide ester Z‐Aib‐Ac₁₀c‐Aib‐OtBu) were determined in the crystal state using X‐ray diffraction. The experimental results support the view that β‐bends and 3₁₀‐helices are preferentially adopted by peptides rich in Ac₁₀c, the third largest cycloaliphatic C^α,α‐disubstituted glycine known. This investigation allowed us to complete a detailed conformational analysis of the whole 1‐amino‐cycloalkane‐1‐carboxylic acid (Ac_nc, with n = 3–12) series, which represents the prerequisite for our recent proposal of the ‘Ac_nc scan’ concept.